Experiments are proposed which are intended to determine the acute and chronic effects of opiates in the hippocampus, cortex, and locus coeruleus from both rats and mice. These preparations will enable us to characterize opiate effects both in terms of evoked field responses and single unit firing in response to iontophoresis, pressure ejection and bath perfusion of opiates and opioid peptides. When the character of opiate responses has been determined, we will make comparisons in opiate responses between tolerant/dependent and drug naive animals, between brain regions, and between species and strains of mice. In making such comparisons we will use both intra- and extracellular recording in order to determine 1) direct vs. indirect opiate actions; 2) possible modulation of other transmitter systems, and 3) the involvement of multiple opiate receptors. With reference to tolerance and dependence, we will investigate tissues chronically treated with opiates in situ and in oculo, and in some cases with in oculo grafts made tolerant by local application of morphine. This will enable us to compare the relative importance of systemic effects, changes in afferent activity, and direct effects in the development of tolerance.